A novel approach for prediction of vitamin D status using support vector regression

BACKGROUND Epidemiological evidence suggests that vitamin D deficiency is linked to various chronic diseases. However direct measurement of serum 25-hydroxyvitamin D (25(OH)D) concentration, the accepted biomarker of vitamin D status, may not be feasible in large epidemiological studies. An alternative approach is to estimate vitamin D status using a predictive model based on parameters derived from questionnaire data. In previous studies, models developed using Multiple Linear Regression (MLR) have explained a limited proportion of the variance and predicted values have correlated only modestly with measured values. Here, a new modelling approach, nonlinear radial basis function support vector regression (RBF SVR), was used in prediction of serum 25(OH)D concentration. Predicted scores were compared with those from a MLR model. METHODS Determinants of serum 25(OH)D in Caucasian adults (n = 494) that had been previously identified were modelled using MLR and RBF SVR to develop a 25(OH)D prediction score and then validated in an independent dataset. The correlation between actual and predicted serum 25(OH)D concentrations was analysed with a Pearson correlation coefficient. RESULTS Better correlation was observed between predicted scores and measured 25(OH)D concentrations using the RBF SVR model in comparison with MLR (Pearson correlation coefficient: 0.74 for RBF SVR; 0.51 for MLR). The RBF SVR model was more accurately able to identify individuals with lower 25(OH)D levels (<75 nmol/L). CONCLUSION Using identical determinants, the RBF SVR model provided improved prediction of serum 25(OH)D concentrations and vitamin D deficiency compared with a MLR model, in this dataset.Dr. Guo is funded by an Australian Postgraduate Award. Prof. Lucas is funded by a National Health and Medical Research (NHMRC) Career Development Fellowship and receives research funding from Cancer Australia, NHMRC, and MS Research Australia. Prof. Ponsonby is funded by a NHMRC Research Fellowship and receives research funding from NHMRC and MS Research Australia. The Ausimmune Study was funded by the US National Multiple Sclerosis Society, NHMRC, and MS Research Australia

Electric-Field Guided Precision Manipulation of Catalytic Nanomotors for Cargo Delivery and Powering Nanoelectromechanical Devices

We report a controllable and precision approach in manipulating catalytic nanomotors by strategically applied electric (E-) fields in three dimensions (3-D). With the high controllability, the catalytic nanomotors have demonstrated new versa-tility in capturing, delivering, and releasing of cargos to designated locations as well as in-situ integration with nanome-chanical devices (NEMS) to chemically power the actuation. With combined AC and DC E-fields, catalytic nanomotors can be accurately aligned by the AC E-fields and instantly change their speeds by the DC E-fields. Within the 3-D orthog-onal microelectrode sets, the in-plane transport of catalytic nanomotors can be swiftly turned on and off, and these cata-lytic nanomotors can also move in the vertical direction. The interplaying nanoforces that govern the propulsion and alignment are investigated. The modeling of catalytic nanomotors proposed in previous works has been confirmed quan-titatively here. Finally, the prowess of the precision manipulation of catalytic nanomotors by E-fields is demonstrated in two applications: the capture, transport, and release of cargos to pre-patterned microdocks, and the assembly of catalytic nanomotors on NEMS to power the continuous rotation. The innovative concepts and approaches reported in this work could further advance ideal applications of catalytic nanomotors, e.g. for assembling and powering nanomachines, nano-robots, and complex NEMS devices

Tightrope walking: Using predictors of 25 (OH)D concentration based on multivariable linear regression to infer associations with health risks

The debate on the causal association between vitamin D status, measured as serum concentration of 25-hydroxyvitamin D (25[OH]D), and various health outcomes warrants investigation in large-scale health surveys. Measuring the 25(OH)D concentration for each participant is not always feasible, because of the logistics of blood collection and the costs of vitamin D testing. To address this problem, past research has used predicted 25(OH)D concentration, based on multivariable linear regression, as a proxy for unmeasured vitamin D status. We restate this approach in a mathematical framework, to deduce its possible pitfalls. Monte Carlo simulation and real data from the National Health and Nutrition Examination Survey 2005-06 are used to confirm the deductions. The results indicate that variables that are used in the prediction model (for 25[OH]D concentration) but not in the model for the health outcome (called instrumental variables), play an essential role in the identification of an effect. Such variables should be unrelated to the health outcome other than through vitamin D; otherwise the estimate of interest will be biased. The approach of predicted 25(OH)D concentration derived from multivariable linear regression may be valid. However, careful verification that the instrumental variables are unrelated to the health outcome is required

MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells

background: MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells. methods: Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays. Effect of the altering expression of miR-7 on migration, invasion, proliferation, interaction and underlying molecular mechanism of breast cancer cells and endothelial cells was investigated after treatment with the synthesised mimic of miR-7. Luciferase activity analysis was performed to validate Wave-3 as a novel target of miR-7. results: miR-7 expression was negatively correlated with the stage, grade and survival of the breast cancer patients. There was also differential expression of miRNAs including miR-7 in the breast cancer cells. The synthesised mimic of miR-7 inhibits the motility and wound healing potential of breast cancer cells. The highly metastatic MDA-MB-231 cells are more sensitive to the miR-7 treatment than the poorly invasive MCF-7 cells. Treatment with miR-7 downregulated the expression of EGFR, IGF1R and Wave3 in MDA-MB-231 cells but not in MCF-7 cells. In addition, we further demonstrated that miR-7 inhibited the proliferation, migration and invasion of endothelial cells. And more importantly, miR-7 suppressed the homing and migration of endothelial cells to more aggressive tumour cell conditions. conclusions: Given the dual inhibitory effect of miR-7 on metastatic breast cancer cells alone and the interaction of endothelial cells with the tumour-conditioned microenvironment, we suggest miR-7 may be a new therapeutic candidate for its capacity not only to prevent breast cancer cell spreading but also to inhibit tumour-associated angiogenesis in the metastatic breast cancer

The Evolution of an Invasive Plant, Sorghum halepense L. (Johnsongrass).

From noble beginnings as a prospective forage, polyploid Sorghum halepense (Johnsongrass) is both an invasive species and one of the worlds worst agricultural weeds. Formed by S. bicolor x S. propinquum hybridization, we show S. halepense to have S. bicolor-enriched allele composition and striking mutations in 5,957 genes that differentiate it from representatives of its progenitor species and an outgroup. The spread of S. halepense may have been facilitated by introgression from closely-related cultivated sorghum near genetic loci affecting rhizome development, seed size, and levels of lutein, a photochemical protectant and abscisic acid precursor. Rhizomes, subterranean stems that store carbohydrates and spawn clonal propagules, have growth correlated with reproductive rather than other vegetative tissues, and increase survival of both temperate cold seasons and tropical dry seasons. Rhizomes of S. halepense are more extensive than those of its rhizomatous progenitor S. propinquum, with gene expression including many alleles from its non-rhizomatous S. bicolor progenitor. The first surviving polyploid in its lineage in ∼96 million years, its post-Columbian spread across six continents carried rich genetic diversity that in the United States has facilitated transition from agricultural to non-agricultural niches. Projected to spread another 200-600 km northward in the coming century, despite its drawbacks S. halepense may offer novel alleles and traits of value to improvement of sorghum

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN